tbuckley/cabot-search huggingface dataset:
Blinded-assessment of a solution to evaluate olaparib maintenance treatment efficacy in patients with ovarian cancer from the GINECO/ENGOT PAOLA-1 trial.
Authors: Adrien Buisson, Pierre Saintigny, Pantelis Constantoulakis, Katerina Oikonomaki, Stavroula Samara, Philipp Harter, Sandro Pignata, Antonio Gonzalez Martin, Christian Schauer, Keiichi Fujiwara, Ignace Vergote, Nicoletta Colombo, Eric Pujade-Lauraine, Isabelle Treilleux, Isabelle Laure Ray-Coquard
Journal: Journal of Clinical Oncology (2023)

5588 Background: SOPHiA DDM Dx HRD Solution (SOPHiA GENETICS, SA) combines analysis of genomic instability with mutational status of HRR genes, including BRCA1/2, generated through a single genomic workflow in order to to predict Homologous Recombination Deficiency (HRD) status in ovarian cancer (OvCa) samples. Previous evaluation of SOPHiA DDM Dx HRD Solution demonstrated its results to be highly concordant with a reference HRD method. As part of the ENGOT HRD initiative, we present updated clinical relevance results of SOPHiA DDM Dx HRD Solution. Methods: GINECO/ENGOT-Ov25 PAOLA-1 trial randomized (2:1) 804 patients (pts) to receive after the end of first-line platinum-based chemotherapy either maintenance olaparib+bevacizumab or placebo+bevacizumab for up to 2 years. DNA from a sub-cohort of 384 formalin-fixed paraffin-embedded (FFPE) OvCa pts samples included in the PAOLA-1 clinical trial were analyzed using SOPHiA DDM Dx HRD Solution(*). We combined SOPHiA DDM Dx HRD Solution genomic instability score, with BRCA mutational status obtained from a Clinical Decision Support module, and clinical interpretation of Variants of Unknown Significance to establish the pts HRD status and investigated differences in progression-free survival (PFS) in the olaparib+bevacizumab and placebo+bevacizumab arms between pts with HRD positive or HRD negative test. Results: We determined the HRD status of 98.4% of pts using SOPHiA DDM Dx HRD Solution. The median PFS time for pts with HRD positive tumors was 35.7 months longer in the olaparib+bevacizumab arm than in the placebo+bevacizumab arm (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.25-0.51, p&lt; 0.001), confirming the findings of our previous interim analysis. No significant difference in PFS was observed between treatment arms in pts with HRD negative test (HR, 1.02; 95% CI, 0.71-1.48; p= 0.90). Conclusions: These clinical relevance results from the SOPHiA DDM Dx HRD Solution evaluation on the PAOLA-1 samples further support the value of combining low-pass whole genome and targeted sequencing in a unique workflow for reliable and cost-effective HRD testing and future patient stratification. (*) Comparison data generated using the CE-IVD pipeline with Clinical Decision Support module for BRCA status only available in EU, Switzerland, UK.
Lenvatinib (LEN) combined with tislelizumab (TIS) plus transcatheter arterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (uHCC): A single-arm, phase II clinical trial.
Authors: Xiang Nong, Yu-Mei Zhang, Jing-Chang Liang, Jin-Long Xie, Zhi-Ming Zhang
Journal: Journal of Clinical Oncology (2023)

4111 Background: uHCC still lacks effective treatments, combination of antiangiogenic targeted drugs and immune checkpoint inhibitors showed promising efficacy. TACE induces tumor necrosis and tumor antigen release, may synergize with immunotherapy. This study was to evaluate the efficacy and safety of TACE in combination with TIS and LEN in patients with uHCC. Methods: This study was a single-center, single-arm, open-label phase II exploratory clinical study (NCT05131698). Eligible patients were BCLC C stage and not candidates for surgical resection or liver transplantation, at least one target lesion evaluable, ECOG performance status of ≤ 1, and Child-pugh grade A or B. Enrolled patients received TACE treatment (loplatin + raltitrexed + iodine oil) followed by TIS (200 mg, IV, on Day 1 of a 21-day cycle) and LEN (body weight ≥ 60 kg: 12 mg/day; &lt; 60 kg: 8 mg/day) daily. The primary endpoint was overall response rate (ORR) by mRECIST. The secondary endpoints included disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) and safety. Results: As of December 28, 2022, 31 enrolled patients with uHCC were treated. Median follow-up time is 11.3 months. Among all patients with BCLC C, 28 patients (90.3%) had microvascular invasion and 17 (54.8%) had portal vein tumor thrombus. As assessed by mRECIST, the ORR and DCR were 71.1% and 87.1%, respectively (2 CR, 6.6%; 20 PR, 64.5%; 5 SD, 16.1%), 4 patients developed tumor progression (12.9%). As assessed by RECIST 1.1, the ORR and DCR were 67.7% and 87.1%, respectively (1 CR, 3.2%; 20 PR, 64.5%; 6 SD, 19.4%), 4 patients developed tumor progression (12.9%). The median PFS was 10.2 months（95% CI: 4.5-NA）, and the median OS was not reached. Any grade treatment-emergent adverse events (TEAEs) occurred in 64.5% (20/31) patients. The most common TEAEs were Increased γ-glutamyl transpeptidase (35%), Increased aspartate aminotransferase (32%), thrombopenia (25%). Only 2 patients experienced grade 3 TEAE (pneumonia). No serious adverse events (SAEs) were reported. Conclusions: In this study, TACE combined with TIS and LEN showed preliminary antitumor efficacy and tolerable safety profile in uHCC. Clinical trial information: NCT05131698 . [Table: see text]
Detection of progression and regression of genitourinary cancers by circulating tumor DNA (ctDNA).
Authors: Ujjwal Karki, Bipin Ghimire, Emma Herrman, Mohammad Muhsin Chisti
Journal: Journal of Clinical Oncology (2023)

e16508 Background: Circulating tumor DNA (ctDNA) are short DNA sequences shed by tumor cells into systemic circulation. The sensitivity and specificity of single ctDNA test to predict relapse or recurrence in solid tumor vary widely and the utility of monitoring serial ctDNA trends has not been well-described in genitourinary cancers. Methods: We conducted a retrospective study including adult patients with genitourinary cancers at the hematology-oncology clinic at William Beaumont - Royal Oak and Troy Hospitals, Michigan from, August 2021 to May 2022, who had ctDNA testing done with imaging available for comparison. We evaluated the correlation between ctDNA test, both single test as well as dynamic trends in value over time, with imaging findings. We also calculated lead time for uptrending ctDNA to detect disease progression compared to imaging. Results: 21 total ctDNA test results from eight patient were included in the study; five had renal cell cancer, two had urothelial cancer and one had prostate cancer. The median age at diagnosis was 62 years (Range: 45-82); 90% were Caucasian and 50% were female. Majority (87.5%) had Stage III or IV disease. Out of the 21 total ctDNA samples, all 16 positive ctDNA results had evidence of disease on corresponding imaging: 13 showed progression while 3 showed regression with residual disease compared to prior imaging. Of the 5 negative ctDNA test results, 2 showed no evidence of disease and 3 showed regression with residual disease on corresponding imaging. Sensitivity and specificity of a single positive ctDNA test to detect evidence of disease on imaging was 84.2% and 100%, respectively. Six patients had multiple ctDNA test results with 12 pairs of serial ctDNA values, of which 9 were up-trending, and 3 were down-trending. Both sensitivity and specificity of up-trending ctDNA values to detect progression and down-trending ctDNA values to detect regression on imaging were 100%. Uptrending ctDNA values predicted disease progression with a median lead time of 55.5 days compared to imaging. Conclusions: Given the high sensitivity and specificity of serial ctDNA monitoring to detect disease progression and regression in our study, we conclude that this may be a valid way to reliably monitor for changes in disease status in genitourinary cancers before they become evident on imaging studies. Further clinical studies are needed to prove its utility in detecting immediate changes in disease status and guide therapeutic intervention in genitourinary cancers. [Table: see text] [Table: see text]
Frequency of somatic mutations in solid tumor malignancies from inner city minorities: A single center study.
Authors: Maria Cristina Cuartas Mesa, Thomas Stiles Bemis, Deimante Tamkus, Shweta Gupta
Journal: Journal of Clinical Oncology (2023)

e15149 Background: The treatment landscape for solid tumor malignancies continues to change with identification of predictive biomarker targets by next generation sequencing (NGS). However, data from individuals from racial and ethnic minorities are often underrepresented. To bridge this gap, we examined the frequency of actionable biomarker findings with a treatment target outlined in NCCN guidelines in our inner city minority population at John H. Stroger, Jr. Hospital of Cook County. Methods: We examined patients who had FoundationOne CDx or FoundationOne Liquid CDx reports for our adult patients with a solid tumor malignancy between July 2021 through December 2022. We categorized patients as having an actionable biomarker finding if there was a finding reported with a treatment target with indication in a patient’s tumor type as outlined in NCCN guidelines. Statistics were done using t-test, z-test, and chi square tests. Results: A total of 313 patients had a FoundationOne CDx or FoundationOne Liquid CDx report for a solid tumor malignancy. Median age for the population was 64.6 years (range 20-89 years). The majority of patients were African American (50%), followed by Hispanic (31%), Caucasian (13%) and Asian (6%). There were 149 patients (47.6%) that had an actionable biomarker target in their tumor type. Among the 50 total lung adenocarcinoma patients, 20 (40%) had a driver mutation, with 12 (60%) being African American. In 43 colorectal tumors were tested, 16 (37.2%) were KRAS WT, with 6 being African American, 6 Hispanic, and 4 white. Among 27 prostate cancer samples tested, 7 (25.9%) harbored a homologous recombination repair (HRR) gene mutation. Of the patients without an actionable biomarker in their tumor type, 47 patients (15%) had an actionable biomarker finding approved in another tumor type. Of the patients with biomarker targets in another tumor type, mutations in PIK3CA and HRR genes were among the most frequent findings. There were no statistically significant differences in frequency of actionable biomarkers in patient tumor type between gender (P = 0.31) or race (P = 0.63). Conclusions: Our findings showed that nearly half of our patients had a targetable somatic mutation in their tumor type. Even in patients without an actionable biomarker in their specific cancer, those patients may harbor a biomarker finding with an approved target in another cancer. While sample sizes were small to investigate mutational profiles for specific tumor types, future analysis with more samples will allow for better characterization. These findings support increasing NGS testing to better characterize the tumor mutational profiles for our racially underrepresented population, as well as for identifying potential biomarkers for future studies in other tumor types.
Association of plant-based diet index with quality of life in patients with prostate cancer.
Authors: Stacy Loeb, Qi Hua, Scott Bauer, Stacey A. Kenfield, Alicia K. Morgans, Lorelei A Mucci
Journal: Journal of Clinical Oncology (2023)

5037 Background: Plant-based diets have many health benefits including a lower risk of fatal prostate cancer. Less is known about the relationship between diet and functional outcomes among prostate cancer survivors. We hypothesized that greater consumption of plant-based food after prostate cancer diagnosis is associated with improved quality of life (QOL). Methods: This prospective cohort study included 3,505 participants in the Health Professionals Follow-up Study with non-metastatic prostate cancer (1986-2016). Overall and healthful Plant-based Diet Indices were calculated from food frequency questionnaires with cumulative updating. QOL scores were calculated using the Expanded Prostate Cancer Index Composite. Generalized estimating equations were used to examine associations between Plant-based Diet Indices and 5 QOL domains, adjusted for clinical and demographic factors. Results: Higher Plant-Based Diet Index was associated with improved scores for sexual function, urinary irritation/obstruction, and urinary incontinence among men with prostate cancer. Consuming more healthful plant-based foods was also associated with better scores for bowel function and hormonal/vitality in the age-adjusted models. Results were similar in sensitivity analyses excluding patients with pre-existing erectile dysfunction or lower urinary tract symptoms, and adjusting for use of sexual or urinary medications. A limitation is that no participants followed a strict vegan diet. Conclusions: This prospective study suggests that greater consumption of healthful plant-based foods is associated with modest improvements in QOL domains among patients with prostate cancer. [Table: see text]
Efficacy and safety of transarterial chemoembolization in combination with lenvatinib and tislelizumab for patients with unresectable BCLC-B stage hepatocellular carcinoma classified as beyond up to seven criteria: A retrospective study.
Authors: Song Chen, Wenbo Guo
Journal: Journal of Clinical Oncology (2023)

e16147 Background: Transarterial chemoembolization (TACE) is the preferred therapeutic regimen for patients with intermediated-stage (BCLC-B stage) unresectable hepatocellular carcinoma (uHCC). However, selected patients with high tumor burden have shown improved survival with systemic treatment, including targeted therapy, immunotherapy, or combination of them. This study was to evaluate the efficacy and safety of combination therapy for BCLC-B stage uHCC beyond up to seven criteria. Methods: In total, 120 patients enrolled in the study during 2015-2021, which were divided into 3 groups according to receive different treatment, and each group just comprised 40 patients. One group received treatment with TACE only (T group), and the other two groups received TACE combined with Lenvatinib (T+L group) and TACE combined with Lenvatinib and tislelizumab (T+L+P group) respectively. We retrospectively compared the clinical outcomes including overall survival (OS), progression-free survival (PFS) and tumor response among the three groups. Both PFS and tumor response were based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Besides, adverse events were collected to assess the safety as well. Results: The median duration of follow-up for all the patients was 28 months [95% CI, 22.8-34.2 months]. The median OS (mOS) was 24.2 months among patients in T+L+P group, as compared with15.0 months among patients receiving TACE alone (HR 0.32; 95%CI 0.19-0.55; P&lt;0.001). The mOS was 20.6 months in T+L group (HR in comparison with TACE only, 0.54; 95%CI 0.34-0.85; P=0.008). The mOS was longer in T+L+P group comparing with T+L group (HR 0.49; 95%CI 0.29-0.85, P=0.011). The similar median PFS (mPFS) benefit was also detected among 3 groups (T+L+P vs. T HR 0.35; 95%CI 0.21-0.58; P&lt;0.001. T+L vs. T HR 0.57; 95%CI 0.36-0.90; P=0.007. T+L+P vs. T+L HR 0.53; 95%CI 0.33-0.84; P=0.003). There was no significant statistic difference observed in objective response rate (ORR) and disease control rate (DCR) between each two groups ( P&gt;0.05). Grade 3 or 4 adverse events (AEs) occurred more common in T+L group or T+L+P group, which was mainly due to target-related or immune-related AEs. There was no mortality happened related to treatment. Conclusions: TACE combined with lenvatinib and tislelizumab may significantly improve clinical outcomes both compared with TACE alone and TACE combined with lenvatinib with a manageable safety profile for BCLC-B stage uHCC beyond up to seven criteria. Nevertheless, it is necessary to be validated by means of prospective randomized control studies in future.
<i><i>Tp53</i></i> as a potential therapeutic biomarker in patients with recurrent high-grade glioma treated with anlotinib and temozolomide.
Authors: Chao-Jie Wang, Ming-Mei Yin, Zheng Zhao, Meng-Yi Zhang, Wei-Feng Zhao
Journal: Journal of Clinical Oncology (2023)

e14000 Background: Patients with recurrent high-grade glioma (rHGG) had a dismal prognosis. Previous studies have found that anlotinib is effective in treating rHGG, but there are no predictive biomarkers to select potential beneficiaries. Methods: The clinical and pathological data of patients with rHGG treated with anlotinib and temozolomide (TMZ) in our hospital were collected and analyzed. Treatment response was assessed according to Response Assessment in Neuro-Oncology criteria. Survival was estimated using the Kaplan-Meier curve with the log-rank test. Tumor protein 53 ( TP53), O-6-methylguanine-DNA methyltransferase, and pre-treatment peripheral blood index were evaluated for potential therapeutic biomarkers. Results: From August 2017 to February 2022, 23 eligible patients with rHGG were included in this study. The objective response rate was 52.2% (95% confidence intervals [CI]: 30.6-73.2%), and the disease control rate was 91.3% (95% CI: 72.0-98.9%). The median progress-free survival (PFS) for all patients was 5.3 months (95% CI: 4.9-5.7 months), with a 6-month PFS rate of 30.4% (95% CI: 13.2-52.9%). The median overall survival (OS) and the 12-month OS rate were 11.0 months (95% CI: 9.7-12.3) and 39.1% (95% CI: 19.7-61.5%), respectively. Patients with TP53 wild-type had significantly higher OS than those with TP53 mutant-type (13.0 months [95% CI: 10.5-15.5 months] vs. 9.0 months [95% CI: 7.4-10.6 months], p= 0.009). Multivariate cox proportional hazards analysis showed that TP53 was an independent prognostic biomarker for OS. Conclusions: The present study showed that anlotinib combined with TMZ had a promising efficacy in treating rHGG and TP53 was a potential biomarker to predict prognosis.
Prevalence of hypertension, hyperlipidemia and diabetes in colon cancer patients and its impact on physical health and quality of life reported in the All of Us research program.
Authors: Noah Osei, Yong Eun, Rajaa Mohamed Salih, Rahman Adesoji Olusoji, Meena Ahluwalia
Journal: Journal of Clinical Oncology (2023)

e15515 Background: The NIH All of Us research program is a prospective, nationwide cohort study currently enrolling more than 594,000 people in the United States. Chronic diseases such as hypertension (HTN), type 2 diabetes mellitus (T2DM), and hyperlipidemia (HLD) are associated with increased morbidity and mortality in cancer patients. Few studies have assessed the impact of each illness on colon cancer patients using extensive population data in the United States. In this study, we investigate the prevalence of these disorders in colon cancer patients and how they affect physical health and quality of life using the All of Us research database. Methods: In this cross-sectional study, we included participants from All of Us dataset version 6, which includes data collected between May 6, 2018, and January 1, 2022, who had available electronic health records (EHR) data. We identified individuals with colon cancer using the ICD-9/ICD-10 diagnosis code and then examined the presence of three disease conditions from the EHR data. Each disease's prevalence and odds ratio were calculated among colon cancer patients (N = 2,366) compared to all participants with available EHR data (N = 258,188). Responses to two questions (perception of overall physical health and quality of life) were studied with options scored from 1 (Poor) to 5 (Excellent). We compared the mean scores between colon cancer patients and colon cancer patients with HLD (N = 1,254), T2DM (N = 356), and HTN (N = 1,234). The odds ratio was calculated using unconditional maximum likelihood estimation. The study compared scores using the Wilcoxon rank sum test, with a significance level of P &lt; 0.05. Analysis was performed in the web-based platform Jupyter Notebook using the programming language R. Results: The prevalence of HTN, HLD, and T2DM in participants with colon cancer was 52.3%, 53.0%, and 15.1%, respectively, compared to 21.6%, 22%, and 7.9% in all participants. The calculated odds ratio of HTN, HLD, and T2DM in participants with colon cancer was 4.05 (95% confidence interval: 3.74-4.40), 4.06 (3.74-4.41), and 2.08 (1.86-2.33), respectively. Mean scores of physical health and quality of life were significantly lower in colon cancer with T2DM patients compared to colon cancer patients. However, the scores of participants with colon cancer and HLD or colon cancer and HTN were not significantly different from participants with colon cancer. Conclusions: Our analysis shows that individuals with colon cancer have a higher prevalence of HTN, T2DM, and HLD than all participants in the All of Us database. T2DM in colon cancer patients is associated with poor self-reported physical health and quality of life. This highlights the importance of regular screening and optimal control and management of chronic disorders in patients with colon cancer.
Microscopic residual disease (MRD) monitoring and time to disease recurrence across gastrointestinal (GI) malignancies: A single-institution, real-world study.
Authors: Harrison David Winters, Paul Sackstein, Benjamin Adam Weinberg, Dipanjan Debnath, Xue Geng, Hongkun Wang, Saavan Chintalacheruvu, John Marshall, Aiwu Ruth He, Marcus Smith Noel, Reetu Mukherji
Journal: Journal of Clinical Oncology (2023)

e15518 Background: Circulating tumor DNA (ctDNA) is a powerful tool that can detect early evidence of cancer relapse, or MRD. While most GI MRD studies to date are in colorectal adenocarcinoma (AC), a limited but growing body of evidence supports its use in other GI cancers. We describe the outcomes of patients (pts) with various GI cancers who underwent real-world MRD testing at our institution. Methods: In this retrospective analysis, we identified GI cancer pts with at least 1 tumor-informed ctDNA test (Natera, Inc) ordered between June 2020-August 2022. Descriptive statistics were used to characterize clinicopathologic factors, clinical contexts of ctDNA testing, rates of ctDNA positivity (ctDNA+), and relapse rates. Median relapse-free survival (mRFS) and overall survival (mOS) were calculated using Kaplan-Meier methods, comparison between groups by log-rank test, and hazard ratios (HR) by Cox proportional hazard models. Results: In total, 228 GI cancer pts underwent ctDNA testing for MRD monitoring. Pts had stage I (20.6%), 2 (32.0%), 3 (38.2%), and 4 (9.2%) disease at diagnosis. Testing started after an initial curative therapy attempt in 82% of pts and after a repeat curative attempt for disease recurrence in 18% of pts. The median follow-up time was 15.0 months (mo). ctDNA testing was successful in 222 pts (97.4%). The cancer subtypes, ctDNA, and clinical outcomes are reported (table). Collectively, 61/222 of pts had at least 1 ctDNA+ test, and 59.0% of these pts had relapse on their next scan performed after a median interval of 40 days (IQR 22-70) from the first positive test. Of the 62/222 pts who relapsed, ctDNA detected relapse before imaging in 43 pts (69.4%) with a median lead time of 57 days (IQR 29-128). The relapse rates were 82.0% vs. 7.5%, mRFS 10.8 mo vs. not reached (NR) (HR 18.6; 95% CI 9.8-35.3), and mOS 43.1 mo vs. NR (HR 5.0; 95% CI 1.8-13.9) in anytime-ctDNA+ pts compared to never-ctDNA+ pts. Similar trends were observed in the colon, rectal, and pancreas AC subgroups. Conclusions: ctDNA was utilized successfully across GI cancers and detected relapse before imaging in most pts. Anytime-ctDNA+ status predicted worse outcomes. About 40% of pts had a ctDNA+ test with no evidence of disease on an immediate subsequent scan, highlighting a prevalent “new stage” of high-risk pts that may benefit from novel treatments. [Table: see text]